Selecting Qualified Investigators

The focus of this post will be selecting adequately performing US clinical trial sites for Investigational New Drug studies.  Depending on the nature and size of your clinical trial, you may be targeting private practices, specialists, academic centers, purpose-built dedicated clinical research facilities, or a combination of any of these to find your principal investigator(s) (PI).  Certainly, there is great cost associated with opening and maintaining a study site so you are well advised to be thorough and thoughtful when evaluating the potential investigators.  As monitors, we may provide input on the clinical operations of a study and assist or manage projections of how many and what types of PIs will be selected and this article will discuss some of the important considerations for qualifying and selecting study sites.

As qualified CRAs, we use our instincts and training to predict and choose the most qualified and motivated PIs.

Inevitably, some study centers will perform better than others and deliver the ideal study candidate while strictly adhering to the protocol.  Careful site selection is absolutely critical to limit the time and resources that will be required during study conduct to manage poor performing sites; I refer to my non-enrolling or poor performing study centers as “duds”. Duds require additional monitoring oversight, coaching, and avoidable cost for continued participation, therefore, these sites are often closed before enrollment or conduct is complete.  Closing a non-performing site is an attractive option to suspend the siphoning of time and resources, but forethought and a well-coordinated site selection exercise can help ensure dud sites are never opened in the first place.

Consider the therapeutic area of study and recruit PIs with relevant experience, the right study tools and equipment, access to the target subject population, interest/motivation to recruit, and availability to participate.  

You needn’t only consider PIs with prior clinical trial experience, but you may gain some considerable efficiencies by targeting PIs who have performed well in prior studies and audits.  Some PIs pay to be listed in clinical trial directories, you may be able to obtain names of doctors to approach through online physician directories, reviewing PIs you or your colleagues have worked with in the past, internal company databases, conference attendee lists, patient advocacy groups, journal article author searches, pharmaceutical sales personnel, medical association websites, telephone directories, the internet, trade journals, other networking contacts, etc.

The FDA maintains lists of disqualified investigators and those that are prohibited or restricted to conduct clinical trials.  You can also review any previous warning letters or license restrictions using publically available databases (Click on the hyperlinked text and see additional links below for further information).  Your investigators will need to adhere to all ICH/GCP guidelines and relevant CFR sections including 21 CFR 312.53.  Check your potential PIs against these lists and also gather anecdotal information regarding the investigator from colleagues and the internet. Read physician review websites like yelp.com or clinician directories.  Determine if there have been previous inspections at the study center.  Some doctors have their own websites and you can also search news databases to find information about a potential PI you are considering.

http://www.fda.gov/ICECI/EnforcementActions/FDADebarmentList/default.htm
http://www.fda.gov/ICECI/EnforcementActions/DisqualifiedRestrictedAssuranceList/default.htm
http://www.accessdata.fda.gov/scripts/cder/cliil/

http://silk.nih.gov/public/cbz1bje.@www.orilist.html

Relevant official FDA guidelines are available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM187772.pdf  and Section C of http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070291.pdf

Here is a checklist from one of my trusted colleagues:
http://www.ehow.com/how_2352851_choose-good-clinical-research-investigators.html

Finally, you can contact the physician and his staff to inform them of the trial, determine their interest, and request that they fill out questionnaires or provide a copy of their CV or a summary of their experience.  If you do develop site selection questionnaires you can ask them for their input on the trial design, to describe their facility, to quantify their qualifications/experience/availability/resources/staff, to identify if they have the proper equipment, to comment on their previous clinical trial or audit experience, to give details on their IRB process, to project potential recruitment and access to the target subject population (double check that there aren’t competing trials at the facility or within the same geography www.clinicaltrials.gov), to detail translation and advertising needs, and to inform you of any anticipated barriers to recruitment.  Much of this work can be done via telephone/fax/email but you may want to schedule a time to visit their office and evaluate whether they are a fit for your trial. For more information read my post on Pre-Study Visits.

Beyond the questionnaire, you can use the site selection process to gauge the communication style, organization, and responsiveness of the site staff.  

Beyond the questionnaire, you can use the site selection process to gauge the communication style, organization, and responsiveness of the site staff.  Ensure there are no conflicts of interest, lack of objectivity, or other reasons to avoid a specific PI.  You will be able to determine the PIs experience conducting other sponsored trials, develop a feel for the turnover at the site, and sniff out any additional red flags that may steer you away from choosing that site or anticipate issues that might creep up during conduct.  Be tactful, gracious, and considerate of their time.  The PI will be evaluating whether they want to work with you as well.  It is very much a two-way street since you may be working closely together for a considerable amount of time if they do join the trial.

Good luck selecting qualified investigators. Definitely take the time before the trial starts to be thorough and deliberate with the site selection process.  There is always pressure to get sites up and running as quickly as possible, but you must balance that need with the requirement to spend adequate time selecting qualified investigators. Hopefully spending enough time choosing your PIs will ensure your trials will be easier to enroll, your studies will be conducted with less protocol deviations, and your study team will be more likely to avoid unnecessarily costly “dud” sites and achieve all of your study objectives.

You may also like...from The Lead CRA archives:

• Routine Monitoring Visits March 2008
• Investigative Site Recruitment Plan Sep 2010
• Motivating Study Coordinators Feb 2011